Maehara Y, Tomoda M, Hasuda S, Kabashima A, Tokunaga E, Kakeji Y, Sugimachi K
Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Br J Cancer. 1999 Mar;79(7-8):1255-61. doi: 10.1038/sj.bjc.6690201.
Mutations in the p53 gene, one of the most common genetic alterations in human cancer, are implicated in tumorigenesis and tumour progression. Although p53 protein expression appears to be correlated to prognosis in patients with malignancy, its prognostic role in gastric cancer has remained controversial. We examined the clinical significance of p53 overexpression in 427 patients with gastric cancer, using multivariate analysis. Tumour sections of gastric cancer tissues from these 427 Japanese patients were stained immunohistochemically with monoclonal antibody PAb1801. The presence of p53 expression was statistically compared with clinicopathological features and post-operative survival, using univariate and multivariate analyses. p53 expression was detected in 38.6% (165 out of 427) of these gastric cancers and immunoreactivity was not observed in normal mucosa adjacent to the tumour. A higher rate of p53 detection was observed among large tumours and in those with a prominent depth of invasion, lymphatic and vascular invasion and lymph node involvement. Prognosis was significantly worse for patients with p53-positive-staining tumours. The 5-year survival rate was 62.5% for patients with p53-negative tumours and 43.3% for those with positive malignancies. p53 expression was a significant prognostic factor for node-positive gastric cancers in subjects undergoing treatment with curative resection, as assessed by Cox regression analysis. Thus, the expression of p53 was closely related to the potential for tumour advance and a poorer post-operative prognosis for patients with gastric cancer.
p53基因的突变是人类癌症中最常见的基因改变之一,与肿瘤发生和肿瘤进展有关。尽管p53蛋白表达似乎与恶性肿瘤患者的预后相关,但其在胃癌中的预后作用仍存在争议。我们使用多变量分析研究了427例胃癌患者中p53过表达的临床意义。用单克隆抗体PAb1801对这427例日本患者的胃癌组织肿瘤切片进行免疫组织化学染色。使用单变量和多变量分析,将p53表达的存在情况与临床病理特征及术后生存率进行统计学比较。在这些胃癌中,38.6%(427例中的165例)检测到p53表达,而在肿瘤相邻的正常黏膜中未观察到免疫反应性。在大肿瘤以及侵袭深度显著、有淋巴和血管侵犯及淋巴结受累的肿瘤中,p53检测率更高。p53染色阳性肿瘤患者的预后明显更差。p53阴性肿瘤患者的5年生存率为62.5%,p53阳性恶性肿瘤患者的5年生存率为43.3%。经Cox回归分析评估,p53表达是接受根治性切除治疗的淋巴结阳性胃癌患者的一个显著预后因素。因此,p53的表达与肿瘤进展的可能性密切相关,且与胃癌患者较差的术后预后相关。